The objectives of the proposed research project are to investigate the physiological mechanisms of glucose homeostasis in the neonate and child as compared to the adult and the pathophysiology of these mechanisms in hypoglycemic disorders. The emphasis of this study will concentrate on substrate availability, integrity of hepatic gluco- regulatory enzymatic pathways and hormonal modulation of substrate availability and hepatic enzyme systems. The study primarily will involve the simultaneous and sequential measurement of circulatory concentrations of glucose, lactate, pyruvate, beta-hydroxybutyrate, aceto-acetate, amino acids, insulin, glucagon, growth hormone, and cortisol in neonates, children and adults prior to and at the time of hypoglycemia. In conjunction with these clinical studies, investigations also will be carried out in laboratory animals to further define the role of substrate mobilization and utilization and their regulation as it pertains to gluconeogenesis.